MS Researchers Discover 'Street-Smart' B-Cells That Learn from the Past

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Two new studies suggest that only specific B-cells are at work in multiple sclerosis, and their wandering behavior is surprising researchers.

Two new studies reveal more about the role B-cells play in multiple sclerosis (MS). New evidence shows that a certain type of B-cell travels back and forth across the blood-brain barrier (BBB) and reproduces in the lymph nodes of the head and neck, leading to MS symptoms.

In one study published in Science Translational Medicine, a research team at the University of California, San Francisco, discovered that only one specific subset of B-cells are at work in MS. They examined the spinal fluid of eight MS patients using multicolor flow cytometry, which counts and sorts individual cells and helps identify biomarkers, combined with DNA sequencing technology.

In a separate study, also published in Science Translational Medicine, researchers at Yale University discovered that the B-cells active in MS do not just travel from lymph nodes to the brain as once thought. Their trip across the protective blood-brain barrier is a two-way street.

Street-Smart B-Cells

Researchers don't know what triggers the release of B-cells, but once these cells enter the central nervous system, they begin their misguided attack on the myelin covering that protects nerve cells. Then they travel back out to the rest of the body, the Yale team discovered, where they grow and divide, retaining their memory of whatever initially triggered the MS inflammation.

These street-smart B-cells, once exposed to the MS trigger, continue their destructive cycle, heading back across the BBB to fight again, explained Kevin C. O’Connor, an assistant professor of neurology at the Yale School of Medicine, in an interview with Healthline.

These B-cells make their home in the draining lymph nodes of the head and neck. There they divide and form new B-cells that also remember the MS trigger, so they know their target before they ever leave the lymph nodes to attack myelin in the brain and spinal cord.

“There is a large body of convergent literature, including ours,” O’Connor said, “that has strongly indicated that B-cells play a role in MS.”

But, O'Connor emphasized, these findings don't mean that B-cells are the only culprit in MS. “B-cells and T-cells work hand in hand," he said. "Both contribute to MS disease.”

B-Cells: A New Target for DMTs?

These two studies shed new light on the role of the immune system in MS. Could this have an impact on future targets for disease modifying therapies (DMTs)?

"The more we learn about B-cells in MS, I expect that we will see more targeted therapies that are designed to minimize collateral damage to the immune system,” O’Connor said.

All of the DMTs currently on the market influence a person's immune response in a broad fashion, targeting all T-cells, all B-cells, or the entire immune system to slow or stop the myelin attacks. As a result, DMTs can have unwanted side effects caused by interfering with a person's normal immune responses.

While much about the immune response in MS is still a mystery, learning the habits of this peculiar subset of B-cells provides a window on the MS process that could lead to more focused treatments.

This research is important, O’Connor said, in that “it tells us that the autoimmune response known to reside in the MS central nervous system also resides in the periphery and that it develops in both compartments, but appears to initiate in the periphery.”

This is key because, until now, scientists thought potential DMTs would have to cross the BBB to be effective.

“Now that we know that this response is present in the periphery,” O’Connor said, “targeting it with therapeutics is possible without having to address whether the therapeutic can travel across the BBB.”

To get across the BBB, drugs need to have very small molecules or else, like trying to stuff a medicine ball through a basketball hoop, it just won’t work. But outside of the BBB, a DMT would only need to enter the bloodstream and act on the B-cells between their excursions into the central nervous system, where they are far more accessible in the lymph nodes of the head and neck.

According to O’Connor, since the B-cells appear to be driven by an unknown trigger, or antigen, that prods them into action, “discovering the identity of ‘the MS antigen’ is next.”